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PMID: 1711202 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Retinoid-mediated transcriptional regulation of keratin genes in human epidermal and squamous cell carcinoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 11 ·1991-06-01 ·Pages 4582-6

Stellmach V, Leask A, Fuchs E

Abstract

Vitamin A and other retinoids profoundly inhibit morphological and biochemical features of epidermal differentiation in vivo and in vitro. To elucidate the molecular mechanisms underlying the differential expression of epidermal keratins and their regulation by retinoids, we examined retinoid-mediated changes in total protein expression, protein synthesis, mRNA expression, and transcription in cultured human keratinocytes and in squamous cell carcinoma (SCC-13) cells of epidermal origin. Our studies revealed that the epidermal keratins, K5, K6, K14, and K16, their mRNAs, and their transcripts were diminished relative to actin as a consequence of retinoic acid (RA) treatment. The effects were most pronounced in SCC-13 and were detected as early as 6 hr post-RA treatment, with enhancement over an additional 24-48 hr. Repression was also observed when 5' upstream sequences of K14 or K5 genes were used to drive expression of a chloramphenicol acetyltransferase reporter gene in SCC-13 keratinocytes. Both cell types were found to express mRNAs for the RA receptors alpha and gamma, which may be involved in the RA-mediated transcriptional changes in these cells. The rapid transcriptional changes in epidermal keratin genes were in striking contrast to the previously reported slow transcriptional changes in simple epithelial keratin genes.

MeSH Terms
Carcinoma, Squamous Cell Carrier Proteins/genetics,metabolism Cell Line Cells, Cultured Chloramphenicol O-Acetyltransferase/genetics,metabolism Epidermis/drug effects,physiology Gene Expression Regulation/drug effects Humans Infant, Newborn Keratins/genetics Male RNA, Messenger/drug effects,genetics,metabolism Receptors, Retinoic Acid Transcription, Genetic/drug effects Transfection Tretinoin/pharmacology
Chemicals
Carrier Proteins RNA, Messenger Receptors, Retinoic Acid Tretinoin Keratins Chloramphenicol O-Acetyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stellmach V
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
Leask A
Fuchs E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.11.4582
Published
1991-06-01
Pages
4582-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51709
Subset
IM
Grants
NIAMS NIH HHS · AR31737 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.11.4582 PMC Full Text View journal details
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